Response to Letter Regarding Article “Genetic obesity and the risk of atrial fibrillation: causal estimates from Mendelian randomization”

We thank Dr. Koh for his interest and comments regarding our work. We agree that the relationship between obesity and cardiovascular disease is nuanced and, more specifically, that measures of adiposity beyond body mass index (BMI) may provide incremental prognostic and mechanistic insight. In the context of atrial fibrillation (AF), our publication discusses several potential mechanisms of the identified association between an increased BMI and AF including, for example, the presence of a systemic inflammatory state, as well as more direct influences of ectopic epicardial fat such as perturbation of autonomic function, elaboration of pro-fibrotic adipokines, and induction of oxidative stress pathways.¹ Potentially distinct relationships between adipose subtypes and AF were highlighted in a recent meta-analysis of observational studies, which identified differential associations between overall, abdominal, and epicardial adipose and incident AF.² Further delineation of the association between adipose subtypes and AF risk could provide greater mechanistic and potential therapeutic insight into our understanding of AF pathogenesis.

Nevertheless, while several novel indices of obesity assessment have been proposed, BMI represents a practical, low-cost and easily measurable clinical tool with national data assessment around the world.³ Indeed, measurement of BMI is one of the cornerstones of the American Heart Association’s (AHA) ‘Life’s Simple 7’ metric for cardiovascular health promotion.⁴ As our findings most directly address the primordial prevention of obesity, we believe our study supports ongoing public health efforts from the AHA, World Health Organization, and others to prevent the emergence of obesity for cardiovascular health promotion generally and for atrial fibrillation specifically.